Abstract

Background

Dimebon is a retired non-selective antihistamine drug currently being investigated
as a therapeutic agent for the treatment of Alzheimer's disease (AD). Results from
several completed clinical trials are mixed and contradictory. Proper interpretations
of these clinical observations, as well as future development of dimebon in AD treatment
are complicated by the lack of concrete information on the mechanisms by which dimebon
might benefit AD.

Results

The present studies are designed specifically to assess whether dimebon might modulate
β-amyloid (Aβ)-mediated responses which are central to the development and progression
of AD dementia. We found that dimebon is bioavailable in the brains of mice following
oral administration. AD mice chronically treated with dimebon exhibited a trend of
improvement in spatial memory function without affecting the levels of total Aβ as
well as soluble oligomeric Aβ in the brain. The same trend of behavior improvement
is also seen in wild type animals chronically treated with dimebon.

Conclusion

Collectively, our preclinical studies using the TgCRND8 AD mouse model demonstrated
that dimebon might have some beneficial effect in improving cognitive function independent
of Alzheimer's disease-type Aβ-related mechanisms or global energy metabolism in the
brain. Observations from our study and others suggesting dimebon might improve cognition
in wild type mice and rats raises the possibility that dimebon might be able to benefit
cognitive function in patients with other neurodegenerative disorders, such as Huntington's
disease, or in the aging population. Additional studies will be necessary to clarify
the mechanisms by which dimebon might directly or indirectly benefit cognitive function.